GSEA vs ORA in top WGCNA Modules

#setwd('/afs/inf.ed.ac.uk/user/s17/s1725186/Documents/PhD-Models/FirstPUModel/RMarkdowns')

library(tidyverse) ; library(reshape2) ; library(glue) ; library(plotly) ; library(dendextend)
library(RColorBrewer) ; library(viridis) ; require(gridExtra) ; library(GGally)
library(knitr)

# Gandal dataset
load('./../Data/preprocessed_data.RData')
datExpr = datExpr %>% data.frame
DE_info = DE_info %>% data.frame


# GO Neuronal annotations: regex 'neuron' in GO functional annotations and label the genes that make a match as neuronal
GO_annotations = read.csv('./../Data/genes_GO_annotations.csv')
GO_neuronal = GO_annotations %>% filter(grepl('neuron', go_term)) %>% 
              mutate('ID'=as.character(ensembl_gene_id)) %>% 
              dplyr::select(-ensembl_gene_id) %>% distinct(ID) %>%
              mutate('Neuronal'=1)


# SFARI Genes
SFARI_genes = read_csv('./../../../SFARI/Data/SFARI_genes_01-03-2020_w_ensembl_IDs.csv')
SFARI_genes = SFARI_genes[!duplicated(SFARI_genes$ID) & !is.na(SFARI_genes$ID),]


# Clusterings
clusterings = read_csv('./../Data/clusters.csv')


# Update DE_info with SFARI and Neuronal information
genes_info = DE_info %>% mutate('ID'=rownames(.)) %>% left_join(SFARI_genes, by='ID') %>% 
  mutate(`gene-score`=ifelse(is.na(`gene-score`), 'Others', `gene-score`)) %>%
  left_join(GO_neuronal, by='ID') %>% left_join(clusterings, by='ID') %>%
  mutate(Neuronal=ifelse(is.na(Neuronal), 0, Neuronal)) %>%
  mutate(gene.score=ifelse(`gene-score`=='Others' & Neuronal==1, 'Neuronal', `gene-score`), 
         significant=padj<0.05 & !is.na(padj))


clustering_selected = 'DynamicHybrid'
genes_info$Module = genes_info[,clustering_selected]

dataset = read.csv(paste0('./../Data/dataset_', clustering_selected, '.csv'))
dataset$Module = dataset[,clustering_selected]

top_modules = dataset %>% arrange(desc(MTcor)) %>% filter(abs(MTcor)>0.9) %>% dplyr::pull(Module) %>% 
              unique %>% as.character

# Correct SFARI Scores
dataset$gene.score = genes_info$gene.score


# Load Enrichment Analyses

# GSEA
load('./../Data/GSEA_bonferroni.RData')
GSEA_GO = enrichment_GO
GSEA_DGN = enrichment_DGN
GSEA_DO = enrichment_DO
GSEA_KEGG = enrichment_KEGG
GSEA_Reactome = enrichment_Reactome
GSEA_SFARI = enrichment_SFARI

# ORA
load('./../Data/ORA_bonferroni.RData')
ORA_GO = enrichment_GO
ORA_DGN = enrichment_DGN
ORA_DO = enrichment_DO
ORA_KEGG = enrichment_KEGG
ORA_Reactome = enrichment_Reactome
ORA_SFARI = enrichment_SFARI



SFARI_colour_hue = function(r) {
  pal = c('#FF7631','#FFB100','#E8E328','#8CC83F','#62CCA6','#59B9C9','#b3b3b3','#808080','gray','#d9d9d9')[r]
}

rm(DE_info, GO_annotations, clusterings, getinfo, mart, dds, GO_neuronal, enrichment_GO, enrichment_DO,
   enrichment_DGN, erichment_DO, enrichment_KEGG, enrichment_Reactome)

# FUNCTIONS

compare_methods = function(GSEA_list, ORA_list){
  
  for(top_module in top_modules){
  
    cat(paste0('  \n  \n  \n  \nEnrichments for Module ', top_module, ' (MTcor=', 
               round(dataset$MTcor[dataset$Module==top_module][1],2), '):  \n  \n'))
    
    GSEA = GSEA_list[[top_module]]
    ORA = ORA_list[[top_module]]
    
    cat(paste0('GSEA has ', nrow(GSEA), ' enriched terms  \n'))
    cat(paste0('ORA has  ', nrow(ORA), ' enriched terms  \n'))
    cat(paste0(sum(ORA$ID %in% GSEA$ID), ' terms are enriched in both methods  \n'))
    
    plot_data = GSEA %>% mutate(pval_GSEA = p.adjust) %>% dplyr::select(ID, Description, NES, pval_GSEA) %>%
                inner_join(ORA %>% mutate(pval_ORA = p.adjust) %>% 
                           dplyr::select(ID, pval_ORA, GeneRatio, qvalue), by = 'ID') 
    
    if(nrow(plot_data)>0) print(plot_data %>% mutate(pval_mean = pval_ORA + pval_GSEA) %>% 
                                arrange(pval_mean) %>% dplyr::select(-pval_mean) %>% kable)
  } 
}


plot_results = function(GSEA_list, ORA_list){
  
  l = htmltools::tagList()

  for(i in 1:length(top_modules)){
    
    GSEA = GSEA_list[[top_modules[i]]]
    ORA = ORA_list[[top_modules[i]]]
    
    plot_data = GSEA %>% mutate(pval_GSEA = p.adjust) %>% dplyr::select(ID, Description, NES, pval_GSEA) %>%
                inner_join(ORA %>% mutate(pval_ORA = p.adjust) %>% dplyr::select(ID, pval_ORA), by = 'ID')
    
    if(nrow(plot_data)>5){
      min_val = min(min(plot_data$pval_GSEA), min(plot_data$pval_ORA))
      max_val = max(max(max(plot_data$pval_GSEA), max(plot_data$pval_ORA)),0.05)
      ggp = ggplotly(plot_data %>% ggplot(aes(pval_GSEA, pval_ORA, color = NES)) + 
                     geom_point(aes(id = Description)) + 
                     geom_vline(xintercept = 0.05, color = 'gray', linetype = 'dotted') + 
                     geom_hline(yintercept = 0.05, color = 'gray', linetype = 'dotted') + 
                     ggtitle(paste0('Enriched terms in common for Module ', top_modules[i])) +
                     scale_x_continuous(limits = c(min_val, max_val)) + 
                     scale_y_continuous(limits = c(min_val, max_val)) + 
                     xlab('Corrected p-value for GSEA') + ylab('Corrected p-value for ORA') +
                     scale_colour_viridis(direction = -1) + theme_minimal() + coord_fixed())
      l[[i]] = ggp
    }
  }
  
  return(l)
}

KEGG

compare_methods(GSEA_KEGG, ORA_KEGG)

Enrichments for Module #73B000 (MTcor=0.94):

GSEA has 42 enriched terms
ORA has 4 enriched terms
4 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
hsa05034	Alcoholism	2.459042	0.0058904	0.0000000	54/649	0.0000000
hsa05322	Systemic lupus erythematosus	3.153606	0.0059327	0.0000000	45/649	0.0000000
hsa05202	Transcriptional misregulation in cancer	2.203888	0.0059057	0.0009106	36/649	0.0002912
hsa05203	Viral carcinogenesis	1.947256	0.0058775	0.0556118	35/649	0.0133392

Enrichments for Module #EE8045 (MTcor=0.93):

GSEA has 46 enriched terms
ORA has 4 enriched terms
4 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
hsa05168	Herpes simplex virus 1 infection	2.552720	0.0043657	0.0000008	58/380	4.00e-07
hsa05034	Alcoholism	2.468803	0.0049104	0.0000671	28/380	2.21e-05
hsa05322	Systemic lupus erythematosus	3.116966	0.0051117	0.0000000	27/380	0.00e+00
hsa05203	Viral carcinogenesis	2.006682	0.0048435	0.0030437	27/380	7.53e-04

Enrichments for Module #00B9E3 (MTcor=-0.93):

GSEA has 47 enriched terms
ORA has 4 enriched terms
3 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
hsa05033	Nicotine addiction	2.280163	0.0054286	0.0108575	13/699	0.0041822
hsa04020	Calcium signaling pathway	1.969428	0.0044889	0.0143596	38/699	0.0041822
hsa04728	Dopaminergic synapse	2.211123	0.0047074	0.0828857	27/699	0.0181054

Enrichments for Module #84AD00 (MTcor=-0.93):

GSEA has 37 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods

Reactome

compare_methods(GSEA_Reactome, ORA_Reactome)

Enrichments for Module #73B000 (MTcor=0.94):

GSEA has 170 enriched terms
ORA has 78 enriched terms
76 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
R-HSA-3247509	Chromatin modifying enzymes	2.278873	0.0243207	0.0000002	57/814	0.0000000
R-HSA-4839726	Chromatin organization	2.278873	0.0243207	0.0000002	57/814	0.0000000
R-HSA-9006931	Signaling by Nuclear Receptors	2.381399	0.0243898	0.0000002	55/814	0.0000000
R-HSA-8878171	Transcriptional regulation by RUNX1	2.201971	0.0244490	0.0000006	50/814	0.0000000
R-HSA-157118	Signaling by NOTCH	2.214671	0.0244334	0.0000404	47/814	0.0000006
R-HSA-8939211	ESR-mediated signaling	2.590280	0.0244928	0.0000000	53/814	0.0000000
R-HSA-201681	TCF dependent signaling in response to WNT	2.034284	0.0244125	0.0000857	45/814	0.0000013
R-HSA-2559583	Cellular Senescence	2.480288	0.0246088	0.0000000	58/814	0.0000000
R-HSA-9018519	Estrogen-dependent gene expression	2.977948	0.0247648	0.0000000	45/814	0.0000000
R-HSA-212165	Epigenetic regulation of gene expression	2.462506	0.0247974	0.0000000	42/814	0.0000000
R-HSA-211000	Gene Silencing by RNA	2.604248	0.0247987	0.0000000	43/814	0.0000000
R-HSA-3214847	HATs acetylate histones	2.598060	0.0248199	0.0000000	46/814	0.0000000
R-HSA-68875	Mitotic Prophase	2.803678	0.0248199	0.0000000	45/814	0.0000000
R-HSA-2559580	Oxidative Stress Induced Senescence	2.699026	0.0249135	0.0000000	44/814	0.0000000
R-HSA-1474165	Reproduction	3.018783	0.0249159	0.0000000	48/814	0.0000000
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs	2.515455	0.0249302	0.0000000	40/814	0.0000000
R-HSA-977225	Amyloid fiber formation	3.054978	0.0249353	0.0000000	40/814	0.0000000
R-HSA-1500620	Meiosis	3.047447	0.0249511	0.0000000	45/814	0.0000000
R-HSA-73864	RNA Polymerase I Transcription	2.759782	0.0249660	0.0000000	40/814	0.0000000
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis	3.005654	0.0249660	0.0000000	40/814	0.0000000
R-HSA-5619507	Activation of HOX genes during differentiation	3.005654	0.0249660	0.0000000	40/814	0.0000000
R-HSA-5578749	Transcriptional regulation by small RNAs	2.925635	0.0250196	0.0000000	41/814	0.0000000
R-HSA-5250913	Positive epigenetic regulation of rRNA expression	2.789580	0.0250196	0.0000000	40/814	0.0000000
R-HSA-427413	NoRC negatively regulates rRNA expression	2.815700	0.0250196	0.0000000	39/814	0.0000000
R-HSA-3214815	HDACs deacetylate histones	3.027939	0.0250215	0.0000000	42/814	0.0000000
R-HSA-73854	RNA Polymerase I Promoter Clearance	2.732154	0.0250247	0.0000000	40/814	0.0000000
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)	3.033487	0.0250294	0.0000000	44/814	0.0000000
R-HSA-1912422	Pre-NOTCH Expression and Processing	3.120790	0.0250294	0.0000000	43/814	0.0000000
R-HSA-5250941	Negative epigenetic regulation of rRNA expression	2.768677	0.0250294	0.0000000	40/814	0.0000000
R-HSA-912446	Meiotic recombination	3.195567	0.0250397	0.0000000	40/814	0.0000000
R-HSA-73772	RNA Polymerase I Promoter Escape	2.995694	0.0250505	0.0000000	39/814	0.0000000
R-HSA-5250924	B-WICH complex positively regulates rRNA expression	2.968917	0.0250505	0.0000000	39/814	0.0000000
R-HSA-5625740	RHO GTPases activate PKNs	3.100816	0.0250673	0.0000000	41/814	0.0000000
R-HSA-1912408	Pre-NOTCH Transcription and Translation	3.192122	0.0250673	0.0000000	39/814	0.0000000
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	3.120711	0.0250673	0.0000000	38/814	0.0000000
R-HSA-2299718	Condensation of Prophase Chromosomes	3.346491	0.0250763	0.0000000	38/814	0.0000000
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)	2.460174	0.0250763	0.0000079	23/814	0.0000001
R-HSA-212300	PRC2 methylates histones and DNA	3.227406	0.0250861	0.0000000	39/814	0.0000000
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere	2.897203	0.0250861	0.0000020	24/814	0.0000000
R-HSA-774815	Nucleosome assembly	2.897203	0.0250861	0.0000020	24/814	0.0000000
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex	3.071049	0.0250927	0.0000000	38/814	0.0000000
R-HSA-73884	Base Excision Repair	2.546982	0.0250805	0.0000145	26/814	0.0000002
R-HSA-3214841	PKMTs methylate histone lysines	2.710487	0.0251059	0.0000000	29/814	0.0000000
R-HSA-5334118	DNA methylation	3.354489	0.0251134	0.0000000	37/814	0.0000000
R-HSA-73728	RNA Polymerase I Promoter Opening	3.315263	0.0251134	0.0000000	37/814	0.0000000
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	3.404989	0.0251148	0.0000000	37/814	0.0000000
R-HSA-1221632	Meiotic synapsis	2.972464	0.0251148	0.0000000	27/814	0.0000000
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	3.166086	0.0251176	0.0000000	38/814	0.0000000
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence	2.789390	0.0251223	0.0000000	28/814	0.0000000
R-HSA-73929	Base-Excision Repair, AP Site Formation	2.892719	0.0251228	0.0000000	24/814	0.0000000
R-HSA-427359	SIRT1 negatively regulates rRNA expression	3.250592	0.0251285	0.0000000	38/814	0.0000000
R-HSA-3214858	RMTs methylate histone arginines	2.859401	0.0251318	0.0000000	39/814	0.0000000
R-HSA-157579	Telomere Maintenance	2.672800	0.0251318	0.0000037	25/814	0.0000001
R-HSA-110328	Recognition and association of DNA glycosylase with site containing an affected pyrimidine	2.921933	0.0251435	0.0000000	24/814	0.0000000
R-HSA-110329	Cleavage of the damaged pyrimidine	2.921933	0.0251435	0.0000000	24/814	0.0000000
R-HSA-73928	Depyrimidination	2.921933	0.0251435	0.0000000	24/814	0.0000000
R-HSA-3214842	HDMs demethylate histones	2.973280	0.0251648	0.0000000	31/814	0.0000000
R-HSA-110330	Recognition and association of DNA glycosylase with site containing an affected purine	3.020401	0.0251918	0.0000000	24/814	0.0000000
R-HSA-110331	Cleavage of the damaged purine	3.020401	0.0251918	0.0000000	24/814	0.0000000
R-HSA-73927	Depurination	3.020401	0.0251918	0.0000000	24/814	0.0000000
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2.396526	0.0251252	0.0000692	23/814	0.0000010
R-HSA-73886	Chromosome Maintenance	2.483760	0.0249846	0.0002307	27/814	0.0000033
R-HSA-5693606	DNA Double Strand Break Response	2.396061	0.0251318	0.0000919	23/814	0.0000013
R-HSA-171306	Packaging Of Telomere Ends	3.053194	0.0252883	0.0000000	23/814	0.0000000
R-HSA-195258	RHO GTPase Effectors	1.840488	0.0241978	0.0012650	54/814	0.0000171
R-HSA-1266695	Interleukin-7 signaling	2.306149	0.0253327	0.0004422	14/814	0.0000062
R-HSA-69473	G2/M DNA damage checkpoint	2.341737	0.0249683	0.0014260	24/814	0.0000191
R-HSA-5693607	Processing of DNA double-strand break ends	2.341501	0.0249725	0.0026772	24/814	0.0000353
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2.235138	0.0248641	0.0223680	27/814	0.0002827
R-HSA-2262752	Cellular responses to stress	1.632674	0.0477761	0.0000079	73/814	0.0000001
R-HSA-195721	Signaling by WNT	1.690092	0.0484043	0.0001708	57/814	0.0000025
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	2.497601	0.0250439	0.0345609	21/814	0.0004310
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	2.093088	0.0245655	0.0462864	33/814	0.0005697
R-HSA-194315	Signaling by Rho GTPases	1.594680	0.0715557	0.0064006	67/814	0.0000820
R-HSA-5693538	Homology Directed Repair	2.171556	0.0248447	0.0534816	27/814	0.0006497
R-HSA-2990846	SUMOylation	2.007948	0.0245606	0.0925865	33/814	0.0011103

Enrichments for Module #EE8045 (MTcor=0.93):

GSEA has 204 enriched terms
ORA has 76 enriched terms
73 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
R-HSA-3247509	Chromatin modifying enzymes	2.382042	0.0195119	0.0000001	43/495	0.0000000
R-HSA-4839726	Chromatin organization	2.382042	0.0195119	0.0000001	43/495	0.0000000
R-HSA-9006931	Signaling by Nuclear Receptors	2.206897	0.0196781	0.0001857	35/495	0.0000025
R-HSA-8878171	Transcriptional regulation by RUNX1	2.261105	0.0198763	0.0000101	35/495	0.0000001
R-HSA-8939211	ESR-mediated signaling	2.449368	0.0200212	0.0000071	34/495	0.0000001
R-HSA-2559583	Cellular Senescence	2.295883	0.0202788	0.0000003	34/495	0.0000000
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	2.071740	0.0203379	0.0000953	29/495	0.0000013
R-HSA-2990846	SUMOylation	1.979695	0.0202852	0.0002019	29/495	0.0000027
R-HSA-157118	Signaling by NOTCH	1.951114	0.0198181	0.0006943	32/495	0.0000091
R-HSA-5693532	DNA Double-Strand Break Repair	2.018206	0.0205764	0.0001818	27/495	0.0000025
R-HSA-212165	Epigenetic regulation of gene expression	2.555835	0.0208463	0.0000005	29/495	0.0000000
R-HSA-9018519	Estrogen-dependent gene expression	2.861305	0.0208499	0.0000000	32/495	0.0000000
R-HSA-3214847	HATs acetylate histones	2.695651	0.0209365	0.0000002	29/495	0.0000000
R-HSA-68875	Mitotic Prophase	2.687889	0.0209365	0.0000008	28/495	0.0000000
R-HSA-211000	Gene Silencing by RNA	2.636333	0.0209926	0.0000003	28/495	0.0000000
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2.229659	0.0210738	0.0000847	24/495	0.0000012
R-HSA-1474165	Reproduction	2.990888	0.0211577	0.0000017	26/495	0.0000000
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs	2.458849	0.0211600	0.0000014	26/495	0.0000000
R-HSA-5693538	Homology Directed Repair	2.149519	0.0210048	0.0002120	24/495	0.0000028
R-HSA-2559580	Oxidative Stress Induced Senescence	2.542884	0.0212351	0.0000000	29/495	0.0000000
R-HSA-73864	RNA Polymerase I Transcription	2.772099	0.0214081	0.0000001	26/495	0.0000000
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis	2.867060	0.0214081	0.0000001	26/495	0.0000000
R-HSA-5619507	Activation of HOX genes during differentiation	2.867060	0.0214081	0.0000001	26/495	0.0000000
R-HSA-73854	RNA Polymerase I Promoter Clearance	2.753275	0.0214122	0.0000000	26/495	0.0000000
R-HSA-1500620	Meiosis	3.041621	0.0214335	0.0000001	26/495	0.0000000
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)	2.919696	0.0214362	0.0000000	29/495	0.0000000
R-HSA-1912422	Pre-NOTCH Expression and Processing	2.995518	0.0214362	0.0000000	26/495	0.0000000
R-HSA-5250941	Negative epigenetic regulation of rRNA expression	2.813435	0.0214362	0.0000002	25/495	0.0000000
R-HSA-5250913	Positive epigenetic regulation of rRNA expression	2.745753	0.0214971	0.0000000	26/495	0.0000000
R-HSA-427413	NoRC negatively regulates rRNA expression	2.872722	0.0214971	0.0000001	25/495	0.0000000
R-HSA-5578749	Transcriptional regulation by small RNAs	2.865456	0.0214971	0.0000001	25/495	0.0000000
R-HSA-73886	Chromosome Maintenance	2.490931	0.0215019	0.0000001	25/495	0.0000000
R-HSA-5693607	Processing of DNA double-strand break ends	2.388162	0.0216587	0.0000002	24/495	0.0000000
R-HSA-977225	Amyloid fiber formation	2.976874	0.0216948	0.0000001	24/495	0.0000000
R-HSA-69473	G2/M DNA damage checkpoint	2.394096	0.0217515	0.0000005	23/495	0.0000000
R-HSA-3214815	HDACs deacetylate histones	3.183673	0.0217741	0.0000000	26/495	0.0000000
R-HSA-1912408	Pre-NOTCH Transcription and Translation	3.167742	0.0218376	0.0000000	26/495	0.0000000
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	3.142486	0.0218376	0.0000000	26/495	0.0000000
R-HSA-5625740	RHO GTPases activate PKNs	3.092663	0.0218376	0.0000000	24/495	0.0000000
R-HSA-5250924	B-WICH complex positively regulates rRNA expression	2.945840	0.0218633	0.0000000	25/495	0.0000000
R-HSA-73772	RNA Polymerase I Promoter Escape	3.024781	0.0218633	0.0000000	24/495	0.0000000
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex	2.931072	0.0218740	0.0000000	26/495	0.0000000
R-HSA-73884	Base Excision Repair	2.481520	0.0218801	0.0000001	23/495	0.0000000
R-HSA-912446	Meiotic recombination	3.177327	0.0220402	0.0000000	24/495	0.0000000
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence	2.845834	0.0220842	0.0000000	23/495	0.0000000
R-HSA-5693606	DNA Double Strand Break Response	2.658132	0.0220896	0.0000000	23/495	0.0000000
R-HSA-157579	Telomere Maintenance	2.678335	0.0220896	0.0000000	23/495	0.0000000
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2.669142	0.0220969	0.0000000	23/495	0.0000000
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	3.166898	0.0221338	0.0000000	25/495	0.0000000
R-HSA-3214858	RMTs methylate histone arginines	2.745707	0.0220896	0.0000751	18/495	0.0000011
R-HSA-1221632	Meiotic synapsis	3.021587	0.0221711	0.0000000	25/495	0.0000000
R-HSA-3214841	PKMTs methylate histone lysines	2.560910	0.0221843	0.0000000	21/495	0.0000000
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere	2.832629	0.0221954	0.0000000	25/495	0.0000000
R-HSA-774815	Nucleosome assembly	2.832629	0.0221954	0.0000000	25/495	0.0000000
R-HSA-212300	PRC2 methylates histones and DNA	3.195257	0.0221954	0.0000000	24/495	0.0000000
R-HSA-2299718	Condensation of Prophase Chromosomes	3.267881	0.0222082	0.0000000	24/495	0.0000000
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)	2.633793	0.0222082	0.0000000	24/495	0.0000000
R-HSA-427359	SIRT1 negatively regulates rRNA expression	3.259000	0.0223359	0.0000000	23/495	0.0000000
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	3.428710	0.0224452	0.0000000	24/495	0.0000000
R-HSA-5334118	DNA methylation	3.406522	0.0225278	0.0000000	23/495	0.0000000
R-HSA-73728	RNA Polymerase I Promoter Opening	3.355613	0.0225278	0.0000000	23/495	0.0000000
R-HSA-73929	Base-Excision Repair, AP Site Formation	2.824304	0.0225502	0.0000000	23/495	0.0000000
R-HSA-110328	Recognition and association of DNA glycosylase with site containing an affected pyrimidine	2.857918	0.0225696	0.0000000	23/495	0.0000000
R-HSA-110329	Cleavage of the damaged pyrimidine	2.857918	0.0225696	0.0000000	23/495	0.0000000
R-HSA-73928	Depyrimidination	2.857918	0.0225696	0.0000000	23/495	0.0000000
R-HSA-3214842	HDMs demethylate histones	2.792860	0.0227196	0.0000056	16/495	0.0000001
R-HSA-110330	Recognition and association of DNA glycosylase with site containing an affected purine	2.955917	0.0227469	0.0000000	23/495	0.0000000
R-HSA-110331	Cleavage of the damaged purine	2.955917	0.0227469	0.0000000	23/495	0.0000000
R-HSA-73927	Depurination	2.955917	0.0227469	0.0000000	23/495	0.0000000
R-HSA-171306	Packaging Of Telomere Ends	3.029616	0.0228412	0.0000000	23/495	0.0000000
R-HSA-195258	RHO GTPase Effectors	1.829443	0.0191205	0.0124005	36/495	0.0001556
R-HSA-201681	TCF dependent signaling in response to WNT	1.685616	0.0398614	0.0025650	30/495	0.0000331
R-HSA-4551638	SUMOylation of chromatin organization proteins	2.046488	0.0442675	0.0000045	19/495	0.0000001

Enrichments for Module #00B9E3 (MTcor=-0.93):

GSEA has 90 enriched terms
ORA has 13 enriched terms
8 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
R-HSA-112316	Neuronal System	2.643595	0.0169280	0.0000000	92/1003	0.0000000
R-HSA-112315	Transmission across Chemical Synapses	2.572379	0.0179982	0.0001390	56/1003	0.0000413
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	2.501833	0.0187214	0.0000146	48/1003	0.0000065
R-HSA-1296071	Potassium Channels	2.209534	0.0204446	0.0020191	27/1003	0.0004499
R-HSA-442755	Activation of NMDA receptors and postsynaptic events	2.413330	0.0206268	0.0036733	25/1003	0.0006548
R-HSA-1296072	Voltage gated Potassium channels	2.533345	0.0222219	0.0164424	15/1003	0.0024423
R-HSA-438064	Post NMDA receptor activation events	2.314038	0.0210213	0.0395355	21/1003	0.0050336
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation	2.398864	0.0233726	0.0665704	10/1003	0.0059330

Enrichments for Module #84AD00 (MTcor=-0.93):

GSEA has 81 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods

Plots of the results when there are more than 5 terms in common between methods:

plot_results(GSEA_Reactome, ORA_Reactome)

Gene Ontology

compare_methods(GSEA_GO, ORA_GO)

Enrichments for Module #73B000 (MTcor=0.94):

GSEA has 0 enriched terms
ORA has 60 enriched terms
0 terms are enriched in both methods

Enrichments for Module #EE8045 (MTcor=0.93):

GSEA has 0 enriched terms
ORA has 43 enriched terms
0 terms are enriched in both methods

Enrichments for Module #00B9E3 (MTcor=-0.93):

GSEA has 61 enriched terms
ORA has 95 enriched terms
31 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
GO:0044297	cell body	2.079677	0.0911222	0.0001105	92/1556	0.0000051
GO:0034762	regulation of transmembrane transport	2.116789	0.0916164	0.0001355	91/1486	0.0000256
GO:0043025	neuronal cell body	2.184071	0.0929181	0.0000414	84/1556	0.0000024
GO:0098793	presynapse	2.655547	0.0931848	0.0000000	96/1556	0.0000000
GO:0008324	cation transmembrane transporter activity	2.158107	0.0932786	0.0000008	86/1474	0.0000001
GO:0015672	monovalent inorganic cation transport	2.246078	0.0934727	0.0000011	87/1486	0.0000005
GO:0034765	regulation of ion transmembrane transport	2.244908	0.0934692	0.0000152	84/1486	0.0000048
GO:0022890	inorganic cation transmembrane transporter activity	2.206956	0.0944116	0.0000004	82/1474	0.0000000
GO:0097060	synaptic membrane	2.405299	0.0946283	0.0000000	99/1556	0.0000000
GO:0098978	glutamatergic synapse	2.459707	0.0959919	0.0000186	72/1556	0.0000013
GO:0033267	axon part	2.619227	0.0960165	0.0000371	71/1556	0.0000023
GO:0022803	passive transmembrane transporter activity	2.060957	0.0971431	0.0000000	74/1474	0.0000000
GO:0015267	channel activity	2.052951	0.0972098	0.0000001	73/1474	0.0000000
GO:0046873	metal ion transmembrane transporter activity	2.109624	0.0980997	0.0000215	64/1474	0.0000015
GO:0022838	substrate-specific channel activity	2.118246	0.0983712	0.0000000	70/1474	0.0000000
GO:0098984	neuron to neuron synapse	2.317062	0.0973726	0.0010876	62/1556	0.0000331
GO:0099572	postsynaptic specialization	2.289442	0.0973726	0.0010876	62/1556	0.0000331
GO:0045211	postsynaptic membrane	2.326902	0.0986545	0.0000000	73/1556	0.0000000
GO:0005216	ion channel activity	2.151565	0.0987311	0.0000000	70/1474	0.0000000
GO:0042391	regulation of membrane potential	2.086443	0.0962160	0.0026710	67/1486	0.0002102
GO:0005874	microtubule	2.056455	0.0960165	0.0033416	65/1556	0.0000952
GO:0050808	synapse organization	2.146128	0.0945592	0.0049189	72/1486	0.0003574
GO:0032279	asymmetric synapse	2.287187	0.0982668	0.0023511	58/1556	0.0000692
GO:0050804	modulation of chemical synaptic transmission	2.364855	0.0947766	0.0066467	71/1486	0.0004484
GO:0099177	regulation of trans-synaptic signaling	2.363625	0.0947335	0.0073571	71/1486	0.0004633
GO:0014069	postsynaptic density	2.260041	0.0985094	0.0066693	56/1556	0.0001841
GO:0023061	signal release	2.161013	0.0945151	0.0238989	70/1486	0.0011339
GO:0030133	transport vesicle	2.225514	0.0968683	0.0250537	59/1556	0.0006707
GO:1904062	regulation of cation transmembrane transport	2.206381	0.0988430	0.0240089	56/1486	0.0011339
GO:0099513	polymeric cytoskeletal fiber	1.741064	0.0917699	0.0583565	78/1556	0.0013219
GO:0050890	cognition	1.969506	0.0998270	0.0905656	51/1486	0.0033379

Enrichments for Module #84AD00 (MTcor=-0.93):

GSEA has 0 enriched terms
ORA has 9 enriched terms
0 terms are enriched in both methods

Plots of the results when there are more than 5 terms in common between methods:

plot_results(GSEA_GO, ORA_GO)

Disease Ontology

compare_methods(GSEA_DO, ORA_DO)

Enrichments for Module #73B000 (MTcor=0.94):

GSEA has 137 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods

Enrichments for Module #EE8045 (MTcor=0.93):

GSEA has 128 enriched terms
ORA has 3 enriched terms
2 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
DOID:1579	respiratory system disease	2.273814	0.0106829	0.0467996	44/363	0.0161951
DOID:0050161	lower respiratory tract disease	2.276961	0.0108113	0.0510984	41/363	0.0161951

Enrichments for Module #00B9E3 (MTcor=-0.93):

GSEA has 111 enriched terms
ORA has 1 enriched terms
1 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
DOID:1826	epilepsy syndrome	2.070965	0.0109172	0.0320472	39/687	0.0320472

Enrichments for Module #84AD00 (MTcor=-0.93):

GSEA has 103 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods

Disease Gene Network

compare_methods(GSEA_DGN, ORA_DGN)

Enrichments for Module #73B000 (MTcor=0.94):

GSEA has 0 enriched terms
ORA has 6 enriched terms
0 terms are enriched in both methods

Enrichments for Module #EE8045 (MTcor=0.93):

GSEA has 49 enriched terms
ORA has 5 enriched terms
1 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
umls:C3495559	Juvenile arthritis	2.37454	0.0496448	0.0196758	34/697	0.0038244

Enrichments for Module #00B9E3 (MTcor=-0.93):

GSEA has 6 enriched terms
ORA has 4 enriched terms
1 terms are enriched in both methods

ID	Description	NES	pval_GSEA	pval_ORA	GeneRatio	qvalue
umls:C0004936	Mental disorders	1.688912	0.0431365	0.0441081	71/1413	0.0147027

Enrichments for Module #84AD00 (MTcor=-0.93):

GSEA has 0 enriched terms
ORA has 0 enriched terms
0 terms are enriched in both methods